Method and system for imaging a biological tissue

ABSTRACT

The present disclosure relates to a method and a system for detecting an anomaly within a biological tissue. A first image of the biological tissue is obtained, the first image containing light at a first wavelength. A second image of the biological tissue is obtained, the second image containing light at a second wavelength. A texture analysis of the biological tissue is performed using spatial information of the first and second images. The texture analysis is resolved over the first and second wavelengths.

CROSS-REFERENCE

The present application is a continuation of U.S. patent applicationSer. No. 17/201,259, filed on Mar. 15, 2021, which is a divisional ofU.S. patent application Ser. No. 16/340,612, filed on Apr. 9, 2019, nowU.S. Pat. No. 10,964,036, issued on Mar. 30, 2021, which is a NationalPhase Entry of International Application Serial No. PCT/162017/056509,filed on Oct. 19, 2017, which claims priority from U.S. ProvisionalPatent Application Ser. No. 62/410,552, filed on Oct. 20, 2016, theentirety of all of which is incorporated by reference herein.

TECHNICAL FIELD

The present disclosure relates to the field of medical imaging. Morespecifically, the present disclosure relates to a method and a systemfor detecting an anomaly within a biological tissue.

BACKGROUND

Imaging techniques are commonly used to assist in the detection anddiagnosis of various illnesses. Images of a particular region ofinterest (ROI) of a subject are analysed to detect anomalies. A commonlyused technique to detect amyloids and other anomalies comprises positronemission tomography (PET) scanning. PET scans are expensive, timeconsuming, and may cause discomfort to the subject.

One example of anomalies that may be detected and lead to theestablishment of a diagnosis comprises amyloids, that is, abnormalprotein aggregates. In particular, while Alzheimer's disease isessentially a neurodegenerative illness, it has been shown that thepresence of amyloid plaques in the retina of a subject may indicate theonset of Alzheimer's disease. It has further been proposed to thediagnosis of other illnesses, for example diabetes and hypertension,could be based on the detection of anomalies within the retina of asubject.

Recently, techniques involving numerical image processing have beenproposed. In particular, image analysis may be used to characterizeimage textures with the aim of discovery abnormal patterns within a ROIof the subject. Currently, there are few commercially availabletechnologies capable of efficiently detecting, within the eye of asubject, a manifestation of a disease rooted in other organs of thesubject. An example of such technology may be found in InternationalPatent Application Publication No. WO 2016/041062 A1 to Sylvestre etal., published on Mar. 23, 2016, the disclosure of which is incorporatedby reference herein in its entirety, which discloses techniques forproducing spectrally resolved images that may be used for identifyingamyloid plaques present in the fundus of a subject suffering from theonset of Alzheimer's disease.

Gray level co-occurrence matrix (GLCM) analysis has been proposed as atool for the representation of the texture of a ROI. For instance, FIG.1 (prior art) is a representation of texture correlations based onspatial GLCM for regions of interest of two subjects, one of which beingamyloid positive. In FIG. 1 , the ROI is within the retina of the twosubjects. Photograph 10 _(A) shows a ROI for an amyloid positive subject(hereinafter patient “A”) while photograph 10 _(B) shows a similar ROIfor an amyloid negative subject (hereinafter patient “B”). Whilephotographs 10 _(A) and 10 _(B) do reveal some differences between theseROIs, these differences are subtle and may not suffice to easilydiscriminate between normal and abnormal conditions. Diagnosis based onphotographs 10 _(A) and 10 _(B) requires the attention of a highlyskilled medical professional. In spite of the skill of the medicalprofessional, diagnosis errors may occur due to the ambiguousdistinction between photographs 10 _(A) and 10 _(B) that respectivelyshow abnormal and normal tissues.

Current imaging techniques tend to provide visual information that canonly be evaluated by highly skilled professionals. Moreover, currentimaging techniques are generally not easily adaptable to the detectionof various types of anomalies in various biological tissues such as ROIsof a subject.

Therefore, there is a need for improvements in the field of medicalimaging that compensate for problems related to the limited adaptabilityof current imaging techniques and to the inherent ambiguity of imagesobtained using such techniques.

SUMMARY

According to the present disclosure, there is provided a method ofdetecting an anomaly within a biological tissue. A first image of thebiological tissue is obtained, the first image containing light at afirst wavelength. A second image of the biological tissue is obtained,the second image containing light at a second wavelength. A textureanalysis of the biological tissue is performed using spatial informationof the first and second images. The texture analysis is resolved overthe first and second wavelengths.

According to the present disclosure, there is also provided a system fordetecting an anomaly within a biological tissue. The system comprises areceiver of a first image and of a second image of the biological tissueand a processor operatively connected to the receiver. The processor isconfigured to perform a texture analysis of the biological tissue usingspatial information of the first and second images, the texture analysisbeing resolved over a first wavelength of the first image and over asecond wavelength of the second image.

According to the present disclosure, there is also provided a method ofdetecting an anomaly within a biological tissue. A monochromatic imageof the biological tissue is obtained. A texture analysis of thebiological tissue is performed using spatial information of themonochromatic image of the biological tissue to identity features of thebiological tissue. A texture image is generated based on the features ofthe biological tissue. The biological tissue of the subject isclassified as normal or abnormal at least in part based on a comparisonbetween first order statistics of the texture image and predeterminedvalues.

The present disclosure further relates to a system for detecting ananomaly within a biological tissue. The system comprises a receiver of amonochromatic image of the biological tissue and a processor operativelyconnected to the receiver. The processor is configured to perform atexture analysis of the biological tissue using spatial information ofthe monochromatic image of the biological tissue to identify features ofthe biological tissue, generate a texture image based on the features ofthe biological tissue, and classify the biological tissue of the subjectas normal or abnormal at least in part based on a comparison betweenfirst order statistics of the texture image and predetermined values.

The foregoing and other features will become more apparent upon readingof the following non-restrictive description of illustrative embodimentsthereof, given by way of example only with reference to the accompanyingdrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments of the disclosure will be described by way of example onlywith reference to the accompanying drawings, in which:

FIG. 1 (prior art) is a representation of texture correlations based onspatial GLCM for regions of interest of two subjects, one of which beingamyloid positive;

FIG. 2 is a schematic representation of a process for using a movingwindow to build a texture image of a biological tissue based on spatialand spectral information;

FIG. 3 is a sequence diagram of a process using GLCM and/or GLRLM and/orMRFM in spatial and spectral directions and using texture information toclassify images of a biological tissue according to an embodiment;

FIG. 4 is a sequence diagram of a process using GLCM and/or GLRLM and/orMRFM in spatial direction and using texture information to classifyimages of a biological tissue according to another embodiment;

FIG. 5 is a high-level network diagram showing elements of a system forclassifying images of the biological tissue;

FIG. 6 is a block diagram of a device for classifying images of thebiological tissue;

FIG. 7 is a representation of texture correlations based on spatial andspectral GLCM for regions of interest of four subjects, two of whichbeing amyloid positive;

FIG. 8 is a histogram of correlation texture-images based on spatial andspectral GLCM for regions of interest of the four subjects of FIG. 7 ;

FIG. 9 is a three-dimensional representation of a statisticalclassification based on spatial and spectral GLCM for the four subjectsof FIG. 7 ; and

FIG. 10 is another three-dimensional representation of a statisticalclassification based on spatial and spectral GLCM for a larger number ofsubjects, the data being obtained following dimensional reduction of thestatistical classification.

Like numerals represent like features on the various drawings.

DETAILED DESCRIPTION

Various aspects of the present disclosure generally address one or moreof the problems related to the limited adaptability of current imagingtechniques and to the inherent ambiguity of images obtained using suchtechniques.

Generally speaking, the present technology adds, to spatial informationinherently present in two-dimensional images, a third dimension definedby the use of spectral information. Images of a biological tissue areobtained in two (2) or more wavelengths. Referring now to the drawings,FIG. 2 is a schematic representation of a process for using a movingwindow to build a texture image, or texture map, of a biological tissuebased on spatial and spectral information. On FIG. 2 , the biologicaltissue is found in a region of interest (ROI) of a subject. An organ ortissue 50 of a subject contains a ROI 52 from which a plurality ofimages 54 ₁, 54 ₂ . . . 54 j are obtained at j distinct wavelengths togenerate a hyperspectral image 56 of the ROI 52. Each one of theplurality of images 54 ₁, 54 ₂ . . . 54 j may be obtained by capturingreflectance or fluorescence emitted from the ROI 52. The images 54 ₁, 54₂ . . . 54 j as well as the hyperspectral image 56 each contain aplurality of pixel rows 58 and a plurality of pixel columns 60. Aportion of the hyperspectral image 56, in a window 62, contains spatialinformation over a width of k pixels and a height of l pixels, in whicheach of k and l are greater than or equal to one (1) pixel, this window62 also containing spectral information 64 defined over the j distinctwavelengths. A texture analysis of the hyperspectral image 56 isperformed based on spatial information contained in the k·l pixels ofthe window 62, the texture analysis being resolved over the j distinctwavelengths. By moving the window 62 over the area of the ROI 52, thetexture analysis provides a texture image 20 _(B) of the ROI 52. Thetexture image 20 _(B) contains information describing the ROI 52, forexample normalised contrast image, normalised homogeneity image,normalised correlation image and/or normalised energy image of the ROI52.

In the context of the present disclosure, a biological tissue mayinclude a region of interest (ROI) and may be as large as a completeorgan or larger, or as small as any tissue or portion thereof sufficientfor the eventual detection of an anomaly and/or for the establishment ofa diagnostic. In a non-limiting example, the biological tissue maycomprise the retina of a subject, or a part thereof, and the anomalybeing searched may comprise the presence of amyloid plaques near a bloodvessel of the retina. In another non-limiting example, the biologicaltissue may be obtained from a biopsy performed on the subject. Imagingof the biological tissue may take place in vivo, ex vivo and/or invitro.

FIG. 3 is a sequence diagram of a process using GLCM and/or GLRLM and/orMRFM in spatial and spectral directions and using texture information toclassify images of a biological tissue according to an embodiment. OnFIG. 3 , a sequence 100 comprises a plurality of operations that may beexecuted in variable order, some of the operations possibly beingexecuted concurrently, some of the operations being optional.

A hyperspectral image of the biological tissue is obtained at operation102. The hyperspectral is composed of a plurality of images of thebiological tissue obtained at a plurality of corresponding wavelengths.At a minimum, two (2) images of the biological tissue are obtained attwo (2) distinct wavelengths. In one variant, the hyperspectral imagemay comprise a third image of the biological tissue containing light ata third wavelength. In another variant, the hyperspectral image maycomprise a larger number of images, each of these images containinglight at a corresponding wavelength. To generate the hyperspectralimage, an image acquisition device (not shown), for example a camera,acquires the first and second images as well as any further image. In anembodiment, the first, second and any further images are obtainedsimultaneously by the image acquisition device. Other image acquisitionmethods such as, in non-limiting examples, successive acquisition ofimages at various wavelengths and scanning laser ophthalmology (SLO)imaging are also contemplated.

Light intensities, or luminance, of the first and second images, and ofany further image if available, may be calibrated at operation 104 tocorrect for eventual power variations over distinct wavelengths causedby imaging equipment providing these images. Likewise, when the imagingequipment does not provide consistent alignment of images at eachwavelength, alignment registration of the first, second and any furtherimages may be made at operation 106 so that corresponding pixels ofthese images correspond to a same element of the biological tissue.Operations 104 and 106 are optional and may not be present inembodiments in which imaging equipment provides calibrated and alignedimages.

A texture analysis of the biological tissue is performed using spatialinformation of at least the first and second images, also using spatialinformation of any further images of the biological tissue if available,the texture analysis being resolved over at least the first and secondwavelengths, and over wavelengths of these further images of thebiological tissue if available. This texture analysis is performed atoperations 108 and 110. For each pixel of the first, second and anyfurther image of the biological tissue, the texture analysis isperformed at operation 108 to identify features of the biological tissueby calculating a matrix, for example using gray level co-occurrencematrix (GLCM), a gray level run length matrix (GLRLM), a Markov RandomField Matrix (MRFM), or any combination of GLCM, GLRLM and MRFM appliedon spatial and spectral information of the first, second and any furtherimage of the biological tissue. A texture value is calculated atoperation 110. Operations 108 and 110 are repeated over pixel rows andpixel columns of the first and second images and of any further image.

In a non-limiting embodiment, the texture image is generated atoperation 112, based on the features of the biological tissue identifiedin the texture analysis of the first, second, and any further images. Aset of biological tissue images, including the first, second and anyfurther images of the biological tissue, is obtained using an imageacquisition device. An image processor implements a moving window havinga j·k·l size. In the moving window, j is a number of wavelengths, alsoequal to the number of images in the set, k is a number of pixels of thewindow in a first dimension of the images of the biological tissue (forexample, along a horizontal width of the biological tissue forming apixel row), and l is a number of pixels of the window in a seconddimension of the images of the biological tissue (for example, along avertical height of the biological tissue forming a pixel column). In aparticular embodiment, l may be equal to one (1) pixel in which case themoving window forms a two-dimensional matrix defined by a number ofwavelengths and a pixel width of the moving window. The texture analysisusing GLCM and/or GLRLM and/or MRFM is performed using informationcontained in this window at an initial position. A value of a specifictexture feature is calculated based on a level of energy, a level ofcorrelation, a level of contrast or a level of homogeneity in the GLCMor GLRLM or MRFM matrix. This value becomes the value of a first pixelof the texture image and thus characterizes the texture. The window isthen moved by a predetermined number of pixels, for example one or morepixels, in space along the first dimension (for example horizontally) onthe set of images of the biological tissue. Information of this windowis again extracted and analysed to define a second pixel of the textureimage. The process continues until the moving window reaches the end ofthe first dimension (the end of a first row) and then continues bydisplacing the moving window by another predetermined number of pixels,for example one or more pixels, along a second dimension (for examplevertically, on another pixel row). The process goes on until the movingwindow has fully covered the set of images or biological tissue.

First order statistics (FOS) based on a histogram of the texture imagemay be calculated at operation 114. The FOS may include any one or moreof intensity mean, intensity skewness, intensity variance and intensitykurtosis of the texture image. The FOS of operation 114 may result inthe determination of a similarity value that can be added to thefeatures of the biological tissue. Optionally, the statisticalinformation obtained at operation 114 may be subject to a supervised orunsupervised dimensional reduction at operation 115, using for exampleone of a principal component analysis (PCA) or a discriminant analysis(DA). The statistical information, with or without dimensionalreduction, is used in the following operation 116, which comprises aclassification of the biological tissue based on its features and,optionally, on the similarity value. The classification may be madeusing any one, or more, of the various FOS found in the texture images,for example a texture reflecting a contrast, correlation, homogeneity,and/or energy. The classification may lead to a negative result 118, inwhich case the biological tissue is classified as normal, or to apositive result 120, in which case the biological tissue is classifiedas abnormal. In more details, the classification made at operation 116may comprise a comparison between predetermined values on one hand, andstatistics of the texture image on the other hand. Alternatively or inaddition, the classification made at operation 116 may compriseidentifying a variation between the texture image or statistics thereofand a previous texture image obtained from a biological tissue of thesame subject, for example the same ROI of the subject, or statisticsthereof. The classification made at operation 116 may also use FOS tocharacterize the variation between the texture image and the previoustexture image. The variation between the texture image and the previoustexture image may be identified after normalization of an intensity ofthe texture image and of an intensity of the previous texture image.Without limitation, the intensity of various pixels of an image may benormalized within an intensity range between 0 and 1, these values beingdimensionless. A progression of the anomaly may be determined at leastin part based on the variation between the texture image and theprevious texture image.

Optionally, operation 122 may further use spectral information of thefirst, second and any further image contained in the hyperspectralimage, at their respective wavelengths, to define a spectral signatureof the biological tissue. The spectral signature is a vector containinginformation of the intensity (i.e. the luminance) of a specific pixelover available wavelengths. This vector may also represent a meanintensity value of a specific region over the available wavelengths. Itbecomes possible to compare the spectral signature with a referencespectral signature from a control biological tissue so that operation116 may further classify the biological tissue of the subject as normal(negative result 118) or abnormal (positive result 120) at least in partbased on this comparison. The classification of the biological tissuemay therefore be supervised and based on reference information, orunsupervised.

The spectral signature may comprise pixel-by-pixel information relatedto the biological tissue. Alternatively, the spectral signature may be amean spectral signature defined over the area of the biological tissueor over a part of the biological tissue. Otherwise stated, the spectralsignature of the biological tissue may be determined at any level ofgranularity useful for the detection of an anomaly and/or for thediagnostic of a condition present in the biological tissue. A comparisonof the spectral signature the biological tissue with the spectralsignature from a control biological tissue or with a spectral signatureobtained from the same or equivalent biological tissue of the subject atan earlier time allows to determine a percentage of differentiation ofthe texture image for every pixel of the biological tissue, It becomespossible to identify a variation between the spectral signature of thebiological tissue and a previous spectral signature obtained from thesame or equivalent biological tissue of the subject, and to determine aprogression of the anomaly at least in part based on the variationbetween the spectral signature of the biological tissue and the previousspectral signature. The determination of the progression of the anomalymay be particularly useful in assessing the effectiveness of a treatmentof the subject

When the classification yields a positive result 120, the sequence 100may continue with one or more operations useful in providing informationabout the anomaly found in the biological tissue to an operator orcaregiver. For instance, an operation 124 may localize the anomalywithin the biological tissue, operation 126 may quantify the anomaly ofthe biological tissue, and operation 128 may provide a visual mapping ofthe biological tissue for display on a computer monitor or similardisplay. Information provided to the operator or caregiver may be usedto establish a diagnosis of the subject at least in part based on thecomparison between the texture image and the reference texture imageand/or on the comparison between the spectral signature of thebiological tissue and the reference spectral signature. Withoutlimitation, the present technology may be used to detect the presence ofbiomarkers, for example biomarkers correlated with cerebral amyloids, inan ROI of the subject. It becomes possible, for example, to detect signsof Alzheimer's disease in the retina of the subject, at least in partbased on the texture analysis of operations 108 and 110 and also basedon results of other operations in the sequence 100. Other illness thatmay become detectable using the operations of the sequence 100 include,without limitation, arteriosclerosis, diabetic retinopathy, glaucoma,age related macular degeneration, skin cancer, and prostate cancer.

FIG. 4 is a sequence diagram of a process using GLCM and/or GLRLM and/orMRFM in spatial direction and using texture information to classifyimages of a biological tissue according to another embodiment. On FIG. 4, a sequence 200 comprises a plurality of operations that may beexecuted in variable order, some of the operations possibly beingexecuted concurrently, some of the operations being optional. Some ofthe operations in the sequence 200 are the same as, or equivalent tosome operations of the sequence 100 and are identified with the samenumerals for consistency. Those operations that are the same as, orequivalent to those described in relation to FIG. 3 are not described indetails for brevity.

In the sequence 200, a texture analysis of the biological tissue isperformed using spatial information of a monochromatic image of thebiological tissue. In one variant, the monochromatic image may beobtained directly at operation 202. In another variant, a hyperspectralimage may be obtained at operation 102, following which a spectraldimension of the hyperspectral image is reduced at operation 204 toprovide the monochromatic image of the biological tissue. This reductionof the spectral dimension may for example be obtained by calculating amean of corresponding pixels at a plurality of wavelengths of thehyperspectral image or through using a principal component analysis(PCA) or a discriminant analysis (DA) of the hyperspectral image.

Regardless of the manner in which the monochromatic image is obtained, atexture analysis of the biological tissue is performed using spatialinformation of the monochromatic image of the biological tissue. Thistexture analysis is performed at operations 206 and 110. For each pixelof the first, second and any further image of the biological tissue, thetexture analysis is performed at operation 108 using gray levelco-occurrence matrix (GLCM), gray level run length matrix (GLRLM),Markov Random Field Matrix (MRFM) or any combination of GLCM, GLRLM andMRFM applied on spatial information of the monochromatic image of thebiological tissue. A texture value is calculated at operation 110.Operations 206 and 110 are repeated over pixel rows and pixel columns ofthe monochromatic image.

Generation of a texture image at operation 112, FOS calculation atoperation 114, dimensional reduction made at operation 115,classification of the biological tissue at operation 116, determinationof the results 118 or 120 and presentation of the results at operations124, 126 and/or 128 are essentially the same as in the foregoingdescription of FIG. 3 , although based on the monochromatic image, andthe results and information obtained from the sequence 200 may be usedfor the same diagnosis purposes as those of sequence 100.

In a non-limiting embodiment, a set of biological tissue images,including first, second and any further images of the biological tissue,is obtained using an image acquisition device. An image processorimplements a moving window having a k·l size. In the moving window, k isa number of pixels of the window in a first dimension of the images ofthe biological tissue (for example, along a horizontal width of thebiological tissue forming a pixel row), while l is a number of pixels ofthe window in a second dimension of the images of the biological tissue(for example, along a vertical height of the biological tissue). Thetexture analysis using GLCM and/or GLRLM and/or MRFM is performed usinginformation contained in this window at an initial position. A value ofa specific texture feature (contrast, energy, correlation orhomogeneity) is calculated. This value becomes the value of a firstpixel of the texture image and thus characterizes the texture. Thewindow is then moved by a predetermined number of pixels, for exampleone or more pixels, in space along the first dimension (for examplehorizontally) on the set of images of the biological tissue. Informationof this window is again extracted and analysed to define a second pixelof the texture image. The process continues until the moving windowreaches the end of the first dimension (the end of a first row) and thencontinues by displacing the moving window by another predeterminednumber of pixels, for example one or more pixels, along the seconddimension (for example vertically, on another pixel row). The processgoes on until the moving window has fully covered the set of images orbiological tissue.

Optionally in the context of the sequence 200, images at variouswavelengths contained in the hyperspectral image obtained at operation102 may be subject to an alignment registration at operation 106, ifneeded to overcome alignment imperfections caused by an imaging devicesupplying the hyperspectral image. Thereafter, operation 122 may usespectral information contained in the hyperspectral image to define aspectral signature of the biological tissue in order to then compare thespectral signature with a reference spectral signature. Then, operation116 may further classify the biological tissue of the subject as normalor abnormal based at least in part on a comparison between the spectralsignature and the reference spectral signature.

In the sequences 100 and 200, each of the operations 102 to 128 and/or202 to 206 may be configured to be processed by one or more processors,the one or more processors being coupled to a memory.

FIG. 5 is a high-level network diagram showing elements of a system forclassifying images of the biological tissue. FIG. 6 is a block diagramof a device for classifying images of the biological tissue. Consideringat once FIGS. 5 and 6 , a network 300 includes device 400 forclassifying images of the biological tissue. The network 300 maycomprise one client device 302 ₁ or a plurality of client devices suchas 302 ₁, 302 ₂ . . . 302 _(n). Each client device 302 comprises animage acquisition device (not specifically shown), for example a camera,a plurality of monochromatic images and/or an hyperspectral image of anROI of a subject. The client devices 302 ₁, 302 ₂ . . . 302 _(n) use adata transfer connection 304 to forward images of biological tissuesfrom their image acquisition devices to the device 400. In turn, thedevice 400 comprises a network interface 402, a processor 404 and mayfurther comprises a memory 406 and a display driver 408. The processor404 implements an image analysis module 410 and a machine learningmodule 412. The device 400 outputs, for a given biological tissue, oneof the negative result 118 or positive result 120 that can betransmitted via the data transfer connection 304 towards the clientdevice 302 having submitted images of the given biological tissue. Thedata transfer connection 304 may comprise, without limitation, theInternet, a cloud network interface, a private network interface, alocal area network, a virtual provide network, and the like. The datatransfer connection 304 may, without limitation, be realized over one ormore wired connection such as optical cables or copper cables, one ormore wireless connections, or any combination thereof.

In more details, the network interface 402 of the device 400 acts as areceiver of a hyperspectral image containing at least a first image anda second image of the biological tissue, or as a receiver of amonochromatic image of the biological tissue.

In the case where the device 400 receives an hyperspectral image, theprocessor 404 may perform an alignment registration of the first andsecond images and any further image contained therein to aligncorresponding pixels of the first, second and any further images thatcorrespond to a same element of the biological tissue. If necessary, theprocessor 404 may calibrate intensities of the first, second and anyfurther images.

In one variant, the processor 404 is configured to perform a textureanalysis of the biological tissue using spatial information of the firstand second images and to resolve the texture analysis over a firstwavelength of the first image and over a second wavelength of the secondimage. In the same or another variant, the processor 404 is configuredto perform a texture analysis of the biological tissue using spatialinformation of the monochromatic image of the biological tissue. Ineither cases, the processor 404 may use a GLCM and/or a GLRLM and/or aMRFM technique to perform the texture analysis. The processor 404 maygenerate a texture image based on the texture analysis of either thefirst and second images or the monochromatic image. The processor 404may then classify the biological tissue of the subject as normal orabnormal at least in part based on a comparison between first orderstatistics of the texture image and predetermined values. The processor404 may also to localise the anomaly within the biological tissue and/orquantify the anomaly. The processor 404 may cause a display (not shown)connected to the display driver 408 to display the texture image. Theprocessor 404 may also cause the network interface 402 to transmit oneor more of the texture image, a classification of the biological tissue,a quantification of a variation from the reference image to the clientdevice having supplied the image or images of the biological tissue.

The memory 406 may store information elements such as statisticalinformation related to anomalies found in the biological tissue, areference texture image of the biological tissue, a previous textureimage obtained from the biological tissue of the same subject, and anycombination thereof. The processor 404 may use this information from thememory 406 in the classification of the biological tissue.

In addition to the features mentioned in the description of FIGS. 5 and6 , the device 400 may further be adapted to execute any one of thefunctions and operations described in the foregoing description of FIGS.4 and 5 , including any combination of these operations.

FIG. 7 is a representation of texture correlations based on spatial andspectral GLCM for regions of interest of four subjects, two of whichbeing amyloid positive. Four (4) photographs were obtained using thetechniques described hereinabove, two (2) of these photographs beingobtained for the same patients “A” and “B”, introduced in the foregoingdescription of FIG. 1 .

Photograph 20 _(A) shows the biological tissue for the amyloid positivepatient “A” while photograph 20 _(B) shows the biological tissue for theamyloid negative “patient B”—photograph 20 _(B) is actually introducedin the foregoing description of FIG. 2 . Comparing photographs 10 _(A)and 20 _(A), and comparing photographs 10 _(B) and 20 _(B), theimprovement in terms of contrast and readability of these images isstriking. Photographs 20 _(C) and 20 _(D) were obtained for two (2)other subjects, patients “C” and “D”; in particular photograph 20 _(C)represents a similar biological tissue for another amyloid positivesubject while photograph 20 _(D) represents a similar biological tissuefor another amyloid negative subject. Once again, consideringphotographs 20 _(C) and 20 _(D), the techniques disclosed herein providemedical images that have much improved readability when compared tothose obtained using earlier techniques.

FIG. 8 is a histogram of correlation texture-images based on spatial andspectral GLCM for regions of interest of the four subjects of FIG. 7 .Curves 30 _(A), 30 _(C), 30 _(B) and 30 _(D) show that pixel intensityreaches high peaks for large numbers of pixels in the cases of the two(2) amyloid positive patients “A” and “C”, such peaks being absent inthe case of the two (2) amyloid negative patients “B” and “D”.

FIG. 9 is a three-dimensional representation of a statisticalclassification based on spatial and spectral GLCM for the four subjectsof FIG. 7 . Results of a first order statistics (FOS) calculation basedon the mean value of the homogeneity image, correlation image and energyimage based on spatial GLCM are shown on the graph of FIG. 9 , whereinthree (3) axes provide mean correlation, mean homogeneity and meanenergy of images formed of reflectance emissions from biological tissuesof these patients. The amyloid positive patients “A” and “C” arerepresented by corresponding points 40 _(A) and 40 _(C) in the 3D spaceof FIG. 9 while the amyloid negative patients “B” and “D” arerepresented by corresponding points 40 _(B) and 40 _(D). A very cleardistinction appears between the positions of amyloid negative orpositive patients within the 3D space, demonstrating the effectivenessof the procedure of FIG. 4 in detecting anomalies within biologicaltissues of those patients. FIG. 9 shows mean values for the correlation,homogeneity and energy of the biological tissue images. Though notillustrated, it is possible to build similar graphs showing thekurtosis, the skewness or the variance of the contrast, correlation,homogeneity and energy of the biological tissue images.

Referring again to FIGS. 3 and 4 , optionally, a dimensional reductionoperation 115 may be applied on the statistical information obtained atoperation 114, before classification of the biological tissue atoperation 116. FIG. 10 is another three-dimensional representation of astatistical classification based on spatial and spectral GLCM for alarger number of subjects, the data being obtained following dimensionalreduction of the statistical classification. Comparing the graph of FIG.10 with the graph of FIG. 9 , a larger number of subjects is used toproduce a first cloud 70 of positive results and a second cloud 72 ofnegative results. The results are obtained following a selection ofthree (3) most important components of a discriminant analysis (DA) atoperation 115.

Those of ordinary skill in the art will realize that the description ofthe method and system for detecting an anomaly within a biologicaltissue are illustrative only and are not intended to be in any waylimiting. Other embodiments will readily suggest themselves to suchpersons with ordinary skill in the art having the benefit of the presentdisclosure. Furthermore, the disclosed method and system may becustomized to offer valuable solutions to existing needs and problemsrelated to the limited adaptability of current imaging techniques and tothe inherent ambiguity of images obtained using such techniques. In theinterest of clarity, not all of the routine features of theimplementations of method and system are shown and described. Inparticular, combinations of features are not limited to those presentedin the foregoing description and combinations of elements listed in theappended claims form an integral part of the present disclosure. Itwill, of course, be appreciated that in the development of any suchactual implementation of the method and system, numerousimplementation-specific decisions may need to be made in order toachieve the developer's specific goals, such as compliance withapplication-, system-, and business-related constraints, and that thesespecific goals will vary from one implementation to another and from onedeveloper to another. Moreover, it will be appreciated that adevelopment effort might be complex and time-consuming, but wouldnevertheless be a routine undertaking of engineering for those ofordinary skill in the field of medical imaging having the benefit of thepresent disclosure.

In accordance with the present disclosure, the components, processoperations, and/or data structures described herein may be implementedusing various types of operating systems, computing platforms, networkdevices, computer programs, and/or general purpose machines. Inaddition, those of ordinary skill in the art will recognize that devicesof a less general purpose nature, such as hardwired devices, fieldprogrammable gate arrays (FPGAs), application specific integratedcircuits (ASICs), or the like, may also be used. Where a methodcomprising a series of operations is implemented by a computer or amachine and those operations may be stored as a series of instructionsreadable by the machine, they may be stored on a tangible medium.

Systems and modules described herein may comprise software, firmware,hardware, or any combination(s) of software, firmware, or hardwaresuitable for the purposes described herein. Software and other modulesmay reside on servers, workstations, personal computers, computerizedtablets, personal digital assistants (PDA), and other devices suitablefor the purposes described herein. Software and other modules may beaccessible via local memory, via a network, via a browser or otherapplication or via other means suitable for the purposes describedherein. Data structures described herein may comprise computer files,variables, programming arrays, programming structures, or any electronicinformation storage schemes or methods, or any combinations thereof,suitable for the purposes described herein.

The present disclosure has been described in the foregoing specificationby means of non-restrictive illustrative embodiments provided asexamples. These illustrative embodiments may be modified at will. Thescope of the claims should not be limited by the embodiments set forthin the examples, but should be given the broadest interpretationconsistent with the description as a whole.

What is claimed is:
 1. A method for imaging a biological tissue,comprising: obtaining, at a receiver, a first image of the biologicaltissue, the first image containing light at a first wavelength;obtaining, at a receiver, a second image of the biological tissue, thesecond image containing light at a second wavelength; and performing, bya processor, a texture analysis of the biological tissue using spatialinformation of the first and second images, the texture analysis beingresolved over the first and second wavelengths.
 2. The method of claim1, wherein each of the first and second images comprises a plurality ofpixel rows and a plurality of pixel columns, the method, furthercomprising performing an alignment registration of the first and secondimages, whereby corresponding pixels of the first and second imagescorrespond to a same element of the biological tissue.
 3. The method ofclaim 1, wherein the texture analysis is performed using a techniqueselected from gray level co-occurrence matrix (GLCM), a gray level runlength matrix (GLRLM), a Markov Random Field Matrix (MRFM) and acombination thereof, the method further comprising generating a textureimage based on features of the biological tissue.
 4. The method of claim3, wherein the features of the biological tissue are identified based onan element selected from a level of contrast of the GLCM or GLRLM orMRFM matrix, a level of correlation of the GLCM or GLRLM or MRFM matrix,a level of homogeneity of the GLCM or GLRLM or MRFM matrix, a level ofenergy of the GLCM or GLRLM or MRFM matrix, and a combination thereof.5. The method of claim 3, further comprising: defining a moving windowhaving a j·k·l size, wherein j is a number of images of the biologicaltissue, wherein k is a number of pixels of the moving window defined ina first dimension of the images of the biological tissue, and wherein lis a number of pixels of the moving window defined in a second dimensionof the images of the biological tissue; using information from theimages of the biological tissue contained in the moving window tocalculate a value of a pixel of the texture image; successivelydisplacing the moving window by a first predetermined number of pixelsin the first dimension of the biological tissue; repeating thecalculation of pixel values of the texture image following eachdisplacement of the moving window in the first dimension of the imagesof the biological tissue; successively displacing the moving window by asecond predetermined number of pixels in the second dimension of theimages of the biological tissue; and repeating the calculations of pixelvalues of the texture image and the displacements of the moving windowover the first dimension of the images of the biological tissuefollowing each displacement of the moving window over the seconddimension of the images of the biological tissue.
 6. The method of claim3, further comprising classifying the biological tissue of the subjectas normal or abnormal at least in part based on a comparison betweenfirst order statistics of the texture image and predetermined values. 7.The method of claim 6, further comprising performing a dimensionalreduction of the first order statistics in view of classifying thebiological tissue of the subject as normal or abnormal.
 8. The method ofclaim 3, further comprising identifying a variation between the textureimage and a previous texture image obtained from the biological tissueof the subject.
 9. The method of claim 3, further comprising classifyingthe biological tissue of the subject as normal or abnormal at least inpart based on a comparison between the texture image and a referencetexture image.
 10. The method of claim 6, wherein the first orderstatistics are selected from intensity mean, intensity skewness,intensity variance, intensity kurtosis and a combination thereof. 11.The method of claim 1, further comprising defining a spectral signatureof the biological tissue using spectral information of the first andsecond images at their respective wavelengths.
 12. The method of claim1, further comprising: obtaining an added plurality images of thebiological tissue, each of the added plurality of images containinglight at a corresponding one of an added plurality of wavelengths;wherein the texture analysis is performed using spatial information ofthe first, second and added plurality of images, the texture analysisbeing resolved over the first, second and added plurality ofwavelengths.
 13. The method of claim 1, further comprising detectingpresence of biomarkers in the biological tissue at least in part basedon the texture analysis.
 14. The method of claim 1, further comprisingdetecting, at least in part based on the texture analysis, signs of anillness selected from Alzheimer's disease, arteriosclerosis, diabeticretinopathy, glaucoma, age related macular degeneration, skin cancer,and prostate cancer.
 15. A system for imaging a biological tissue,comprising: a receiver of a first image and of a second image of thebiological tissue; and a processor operatively connected to thereceiver, the processor being configured to: perform a texture analysisof the biological tissue using spatial information of the first andsecond images, the texture analysis being resolved over a firstwavelength of the first image and over a second wavelength of the secondimage.
 16. The system of claim 15, wherein the processor is furtherconfigured to identify, as part of the texture analysis, features of thebiological tissue selected from a level of contrast of the first andsecond images, a correlation of first and second images, a level ofhomogeneity of the first and second images, a level of energy of thefirst and second images, and a combination thereof; generate a textureimage based on the features of the biological tissue; and classify thebiological tissue of the subject as normal or abnormal at least in partbased on a comparison between first order statistics of the textureimage and predetermined values.
 17. The system of claim 15, wherein theprocessor is further configured to localise the anomaly within thebiological tissue.
 18. The system of claim 15, wherein the processor isfurther configured to quantify the anomaly.
 19. The system of claim 15,further comprising a memory operatively connected to the processor, thememory storing information elements selected from statisticalinformation related to anomalies found in the biological tissue, areference texture image of the biological tissue, a previous textureimage obtained from the biological tissue and a combination thereof. 20.The system of claim 15, wherein the processor is further configured tocalibrate intensities of the first and second images.